Disease relevance of DSG3

• Phage lambda genomic clones were obtained containing 4.2 kb upstream of the translation start site of DSG1 and 517 bp upstream of the DSG3 start site [1].
• The human gene (DSG3) coding for the pemphigus vulgaris antigen is, like the genes coding for the other two known desmogleins, assigned to chromosome 18 [2].
• We suggest the unambiguously expressed DSG3 protein to be used as a marker for keratoconus [3].
• Two Dsg are targeted by pathogenic autoantibodies produced in the course of autoimmune bullous skin diseases, Dsg1 in pemphigus foliaceus (PF), and Dsg3 and Dsg1 in pemphigus vulgaris [4].
• Pemphigus vulgaris (PV) is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion caused by the action of autoantibodies against a keratinocyte cell surface glycoprotein, the PV antigen (PVA) [2].

Psychiatry related information on DSG3

• At this reaction time, no further coverage was observed beyond a base/PVA ratio twenty times greater than the stoichiometric ratio [5].

High impact information on DSG3

• Pemphigus vulgaris (PV) is a life-threatening skin disease in which autoantibodies against a keratinocyte cell surface 130 kd glycoprotein, PV antigen (PVA), cause loss of cell-cell adhesion, with resultant epidermal blisters [6].
• We used affinity-purified PV IgG to isolate cDNA, containing the entire coding sequence for PVA, from human keratinocyte expression libraries [6].
• Autoantibodies against the epidermal desmosomal cadherins desmoglein 1 (Dsg1) and Dsg3 have been shown to cause severe to lethal skin blistering clinically defined as pemphigus foliaceus (PF) and pemphigus vulgaris (PV) [7].
• These results indicate that this baculovirus product has the proper conformation of the authentic PVA and that its conformation is important in pathogenicity of pemphigus [8].
• To confirm the specificity of this binding we showed that antibodies raised in rabbits against the extracellular portions of PVA also bound desmosomes in these cultures [9].

Chemical compound and disease context of DSG3

• Pemphigus vulgaris-IgG causes a rapid depletion of desmoglein 3 (Dsg3) from the Triton X-100 soluble pools, leading to the formation of Dsg3-depleted desmosomes in a human squamous carcinoma cell line, DJM-1 cells [10].
• BACKGROUND: Pemphigus vulgaris (PV) shows autoimmune reaction against desmoglein 3 (Dsg3), whereas paraneoplastic pemphigus (PNP) shows autoimmune reaction against Dsg3 as well as numerous members of the plakin family [11].
• The mechanical properties of the tube wall were selected to match a thick-wall stenosis model made of PVA hydrogel [12].
• Plastic straws, of a type widely used for semen cryopreservation, sealed using three different methods, (PVA powder, plastic spheres and plasticine modelling clay) were tested for leakage of low molecular weight dye (methylene blue), bacteria (Escherichia coli) and virus (Newcastle disease virus) [13].
• Pre-treatment with chitosan followed by microsphere treatment (CTS/PVA/TCP) was more effective in decreasing toxicity than the treatment using only chitosan [14].

Biological context of DSG3

• Transient transfections with a series of deletion clones indicated that the DSG3 promoter demonstrated keratinocyte-specific expression, as compared with dermal fibroblasts examined in parallel, and fine mapping identified a 30-base pair segment at -200 to -170 capable of conferring epidermal specific expression [15].
• Primer extension analysis and RNase protection experiments revealed four putative transcription initiation sites for DSG1 at positions -163, -151, -148 and -141, and seven closely linked sites for DSG3, the longest being at -140 relative to the translation start site [1].
• Analysis of the exon/intron organization of the human desmoglein 4 gene (DSG4) demonstrates that it is composed of 16 exons spanning approximately 37 kb of 18q12 and is situated between DSG1 and DSG3 [16].
• In this study, the genes for two autoantigens (DSG1 for pemphigus foliaceus and DSG3 for pemphigus vulgaris) were mapped on band q12 of human chromosome 18 by fluorescence in situ hybridization [17].
• Analysis of 1.9 kb upstream of the translation start site revealed consensus binding sites for transcription factors including Ap-2 and Sp-1, and motifs common to the promoters of other epithelially expressed genes such as keratin 14 and the desmoglein genes DSG1 and DSG3 [18].

Anatomical context of DSG3

• Epithelial cell membrane antigens other than DSG1 or DSG3 are targeted by effectors of PAMS autoimmunity [19].
• In Patients with pemphigus vulgaris, autoantibodies against the desmosomal glycoprotein desmoglein 3 (Dsg3) cause blisters due to loss of keratinocyte cell-cell adhesion in the basal and immediate suprabasal layer of the deeper epidermis, leaving the superficial epidermis intact [20].
• In oral mucosa and esophagus both Dsg were immunoreactive on cell surfaces throughout the entire epithelia, but staining intensity was weaker for Dsg1 than for Dsg3 [21].
• Immunoblotting was performed to compare Dsg1 and Dsg3 expression levels in extracts from epidermis and oral mucosa [21].
• Adsorption with only the Dsg1 extracellular domain left antibodies that stained only the basal and immediate suprabasal layers of the epidermis and immunoprecipitated only Dsg3, not Dsg1, from extracts of cultured cells synthesizing these molecules [20].

Associations of DSG3 with chemical compounds

• These patients were on prednisolone and immunosuppressives at the time the sera were tested, and it is unclear if the transition from PV to PF is a permanent one or whether it is due to preferential suppression of Dsg3 antibodies below a certain threshold [22].
• Immunoblot analysis, using ethylenediamine tetra-acetic acid-separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3 [23].
• Interestingly, only autoantibodies against the Dsg3 NH2-terminal epitope(s) are able to bind human skin [24].
• AK23 mAb increased serine phosphorylation of Dsg3 and augmented activation levels of p38 MAPK [25].
• Of 42 serum samples (25 patients administered carbamazepine, eight patients administered valproic acid and nine healthy volunteers) tested by ELISA, three patients administered carbamazepine showed positive reactivity against both Dsg1 and Dsg3 [26].
• Cholesterol binding agents such as filipin and nystatin and the tyrosine kinase inhibitor genistein dramatically inhibited Dsg3 internalization [27].

Physical interactions of DSG3

• In this study, we examined desmoglein (Dsg) 3 and other desmosomal molecules after pemphigus vulgaris (PV)-immunoglobulin G (IgG) binding to the Dsg3 on the cell surface in DJM-1 cells, a human squamous cell carcinoma cell line [10].
• Immunofluorescence analysis indicated that PV IgG and Dsg3 were rapidly internalized from the cell surface in a complex with plakoglobin but not desmoplakin [28].

Regulatory relationships of DSG3

• TP did not directly block binding of pemphigus IgG to their target Dsg antigens but prevented PV-IgG-induced inhibition of Dsg3 transinteraction in cell-free (atomic force microscopy) and cell-based (laser tweezer) experiments, indicating stabilization of Dsg3 bonds [29].

Other interactions of DSG3

• DSG3 was expressed in association with the cell membrane of the basal and suprabasal epithelial cells, and S100A2 was expressed in the nucleus and cytoplasm, often as intracellular granules [3].
• We now present evidence, using a polymerase chain reaction assay, that DSG3, the gene coding for PVA, is assigned to the same chromosome [2].
• Plakoglobin binding by human Dsg3 (pemphigus vulgaris antigen) in keratinocytes requires the cadherin-like intracytoplasmic segment [30].
• Dsg3 internalization was associated with retraction of keratin filaments from cell-cell borders [28].
• Dsg3-responsive IL-10-secreting Tr1 cells were isolated by MACS cytokine secretion assay from healthy carriers of the PV-associated HLA class II alleles, DRB1*0402 and DQB1*0503, but were only rarely detected in PV patients [31].

Analytical, diagnostic and therapeutic context of DSG3

• In the autoimmune skin diseases pemphigus foliaceous and pemphigus vulgaris (PV), where the autoantigens are, respectively, encoded by the DSG1 and DSG3 genes, severe areas of acantholysis (cell separation), potentially life-threatening in the case of PV, are evident [32].
• The DSG3, S100A2, and SLPI proteins were quantified by Western blotting, and the cellular localization was determined by immunohistochemistry [3].
• We present a 38-year-old Japanese male who showed clinically and histopathologically typical features of pemphigus vulgaris, whose sera reacted with all PVA, PFA, and desmocollins using immunoblotting of both human epidermis and bovine snout epidermis [33].
• METHODS: In 79 subjects with PV, enzyme-linked immunosorbent assays were used to detect IgG autoantibodies reactive with the ectodomain of Dsg1 and Dsg3 [34].
• Both the Dsg3 and Dsg1 ELISAs were more specific and sensitive than conventional immunofluorescence staining [35].

References